Much is still unknown about the basic pathophysiology of diabetes mellitus. Studies in vitro of the type proposed here are directed towards better knowledge of changes occurring at the cellular level. We plan to study insulin synthesis, secretion, and action. We plan to study changes associated with the atherosclerotic, microangiopathic, and nephropathic consequences of diabetes. It has been our feeling that a beta cell preparation essentially free of other cell types is necessary for better understanding of insulin synthesis and release. Our approach has been to obtain a monolayer culture of beta cells; we are currently investigating methods to develop such cultures which are free of fibroblasts. We also are continuing our studies of insulin action on several isolated cell systems: cultured fibroblast, cultured skeletal muscle cell, cultured smooth muscle cell, cultured renal glomeruli, and isolated lymphocyte. We also will investigate the changes occurring with diabetes. In particular, we are interested in changes occurring at the cellular level which lead to atherosclerosis, microangiopathy, and nephropathy. We feel that one of the earliest changes will be in glycoprotein metabolism.